<scp>ELF1</scp> suppresses autophagy to reduce cisplatin resistance via <scp>miR</scp> ‐152‐3p/ <scp>NCAM1</scp> / <scp>ERK</scp> axis in lung cancer cells

Resistance to chemotherapeutic drugs limits the efficacy of chemotherapy in non-small-cell lung cancer (NSCLC). Autophagy is an essential mechanism which involves in drug resistance. Our previous research has revealed that miR-152-3p represses NSCLC progression. However, the mechanism of miR-152-3p in autophagy-mediated chemoresistance in NSCLC remains unclear. Cisplatin-resistant cell lines (A549/DDP and H446/DDP) were transfected with related vectors and subjected to cisplatin, autophagy inhibitor, activator, or extracellular signal-regulated kinase (ERK) activator. Flow cytometry, CCK8 and Colony formation assays were performed for testing apoptosis and cell viability. The related RNAs or proteins were detected by qRT-PCR or western blot. Chromatin immunoprecipitation, luciferase reporter assay or RNA immunoprecipitation were used for validating the interaction between miR-152-3p and ELF1 or NCAM1. CO-IP verified the binding between NCAM1 and ERK. The role of miR-152-3p in cisplatin resistance of NSCLC were also validated in vivo. The results showed that miR-152-3p and ELF1 were decreased in NSCLC tissues. MiR-152-3p reversed cisplatin resistance by inhibiting autophagy through NCAM1. NCAM1 promoted autophagy through ERK pathway and facilitated cisplatin resistance. ELF1 positively regulated miR-152-3p level by directly interacting with miR-152-3p promoter. And miR-152-3p was targeted NCAM1 to regulate NCAM1 level and then affected the binding of NCAM1 to ERK1/2. ELF1 inhibited autophagy and reversed cisplatin resistance through miR-152-3p/NCAM1. MiR-152-3p inhibited autophagy and cisplatin resistance of xenograft tumor in mice. In conclusion, our study revealed that ELF1 inhibited autophagy to attenuate cisplatin resistance through miR-152-3p/NCAM1/ERK pathway in H446/DDP and A549/DDP cells, suggesting a potential novel treatment strategy for NSCLC.